Project Summary/Abstract: Overall The Norris Cotton Cancer Center (NCCC) is responsible for overseeing all cancer-related academic and clinical activities across the entirety of Dartmouth College and the Dartmouth-Hitchcock (D-H) health system, as evidenced by 123 Members spanning 4 Schools and 24 Departments and NCCC-initiated research infrastructure adopted campus-wide. In the current application, we summarize research accomplishments and document fulfillment of the NCI?s Six Essential Characteristics for NCI-Designated Centers. The mission of NCCC is to accelerate trans-disciplinary research to prevent and cure cancer, enhance survivorship, and promote health equity, evident in significant funded patient-centric population science and diversity-focused engagement of trainees across the education continuum. Reflecting deep integration within our host institutions, NCCC is comprised of four truly trans-disciplinary research programs, reflecting active NCCC Planning & Evaluation: Immunology and Cancer Immunotherapy (ICI); Translational Engineering in Cancer (TEC); Cancer Biology and Therapeutics (CBT); and Cancer Population Sciences (CPS). Included in our research portfolio are groundbreaking scientific initiatives in cancer immunology, cancer engineering, biological mechanisms, experimental therapeutics, molecular epidemiology, health care delivery science and cancer prevention and control, with an enhanced emphasis on translating research discoveries to hard-to-reach populations, especially those within our rural two-state catchment area of New Hampshire and Vermont. NCCC continues to be defined by its high impact scientific publications and the frequency with which they are enabled by Cancer Center support of trans-disciplinary research, as evidenced by inter- (31%) and intra-(17%) co- authorships, cancer themes in IDeA-funded program projects, and access to NCCC Shared Resources that include several (e.g., Pathology, Trace Elements, Genomics) relied upon widely by other NCI designated centers. Consistent with our commitment to both high quality science and the successful translation of research discoveries to the clinic, the past five years have witnessed an 18% increase in our NIH-funded research portfolio, including a >7:1 return on Developmental Funds, and a 62% increase in clinical trials accrual, including funding as an NCTN lead participation site. Depth of Leadership was evidenced by accomplishments during a recent Director transition. Shortly following the September 2017 arrival of Dr. Steven Leach as Center Director, NCCC embarked upon a new 2018 Strategic Plan, which identified accelerating translational and trans-disciplinary research as our single highest overarching strategic priority. Emanating from this plan and enabled by a dramatic increase in investment from our parent institutions, in this application we further document the launch of multiple new initiatives in faculty recruitment (8 completed in 2017-2018, 3 active, and 2 pending), faculty research support, education and community outreach, serving to propel a comprehensive NCCC into its fifth decade of NCI designation.